Methylthioadenosine is a sulfur-containing adenine nucleoside produced from S-adenosylmethionine (SAMe) during polyamine biosynthesis. Methylthioadenosine is commonly used in the study of colitis, liver disease, and various cancers[1][2].
Methylthioadenosine (15μM; 3 days) protect MTAP-positive HF cells, but not MTAP-negative A549 cells, from toxic adenine analogs[1]. Methylthioadenosine (1-1000μM; 48h) treatment induced the SKMel147 cell dephosphorylation of the downstream mTOR target S6 ribosomal protein, and the decrease of cyclin D1 protein levels[2]. Methylthioadenosine (50-250µM; 5d) inhibits the proliferation of human CD4+ and CD8+ T cells and the induction of cell cycle progression[3].
In the Male Mdr2−/−-induced hepatocellular carcinoma (HCC) model, Methylthioadenosine (30mg/kg) inhibited inflammatory infiltration in vivo, the expression of cytokines IL6 and Mcp-1, profibrotic factors such as TGFβ2 and tenascin-C, and profibrotic intracellular signaling pathways[4]. In the DSS-induced colitis model in mice, prophylactic administration of Methylthioadenosine (150mg/kg) reduced the activity, body weight, myeloperoxidase activity, and histological damage in colitis mice[5].
References:
[1]. Lubin M, Lubin A. Selective killing of tumors deficient in methylthioadenosine phosphorylase: a novel strategy[J]. PloS one, 2009, 4(5): e5735.
[2]. Andreu-Pérez P, Hernandez-Losa J, Moliné T, et al. Methylthioadenosine (MTA) inhibits melanoma cell proliferation and in vivo tumor growth[J]. BMC cancer, 2010, 10: 1-11.
[3]. Henrich F C, Singer K, Poller K, et al. Suppressive effects of tumor cell-derived 5′-deoxy-5′-methylthioadenosine on human T cells[J]. Oncoimmunology, 2016, 5(8): e1184802.
[4]. Latasa M U, Gil-Puig C, Fernandez-Barrena M G, et al. Oral methylthioadenosine administration attenuates fibrosis and chronic liver disease progression in Mdr2−/− mice[J]. PloS one, 2010, 5(12): e15690.
[5]. Benight N M, Stoll B, Marini J C, et al. Preventative oral methylthioadenosine is anti-inflammatory and reduces DSS-induced colitis in mice[J]. American Journal of Physiology-Gastrointestinal and Liver Physiology, 2012, 303(1): G71-G82.
Methylthioadenosine是多胺生物合成过程中由 S-腺苷甲硫氨酸(SAMe)产生的含硫腺嘌呤核苷。Methylthioadenosine常用于结肠炎、肝病和各种癌症疾病的研究[1][2]。
Methylthioadenosine（15μM；3d）可保护MTAP阳性HF细胞免受毒性腺嘌呤类似物的侵害，但不能保护MTAP阴性A549细胞免受毒性腺嘌呤类似物的侵害[1]。Methylthioadenosine（(1-1000μM；48h）处理可诱导SKMel147细胞下游mTOR靶标S6核糖体蛋白的去磷酸化，并降低细胞周期蛋白D1蛋白水平[2]。Methylthioadenosine（50-250µM；5d）可抑制人类CD4+和 CD8+ T细胞的增殖并诱导细胞周期进展[3]。
在雄性Mdr2−/−诱发的肝细胞癌（HCC）模型中，Methylthioadenosine（30mg/kg）抑制了体内炎症浸润、细胞因子IL6和Mcp-1的表达、抑制了促纤维化因子（如TGFβ2和肌腱糖蛋白-C）以及促纤维化细胞内信号通路[4]。在DSS诱发的小鼠结肠炎模型中，预防性给予Methylthioadenosine（150mg/kg）可降低结肠炎小鼠的活动性、体重、髓过氧化物酶活性和组织学损伤[5]。